Macrocyclic 5-7-membered cyclic

The synthesis of five-, six-, and seven-membered cyclic esters or timides uses intramolecular condensations under the same reaction condifions as described for intermolecular reactions. Yields are generally excellent. An example from the colchicine synthesis of E.E. van Ta-melen (1961) is given below. The synthesis of macrocyclic lactones (macrolides) and lactams (n > 8), however, which are of considerable biochemical and pharmacological interest, poses additional problems because of competing intermolecular polymerization reactions (see p. 246ff.). Inconveniently high dilution, which would be necessary to circumvent this side-... 

Dynamic transacetalization experiments targeting cyclophane formation have also been described by Mandolini and coworkers [34]. Production of a cyclic polyether DCL by direct reaction of triethylene glycol and 4-nitrobenzaldehyde has been reported by Berkovich-Berger and Lemcoff amplification of small macrocyclic members of the library by ammonium ion was observed [35]. With these few examples demonstrating feasibility, we can anticipate increased use of transacetalization in future DCC efforts. 

Imines derived from macrocyclic ketones (C10 to C 15 ) and (- )-(S)-a-(methoxymcthyl)benzene-ethanamine are successfully deprotonated using LDA ( —25 JC. THF. 1 h)9. In contrast to azaenolates of C0- to C8-membered cyclic ketones, which show only E geometry, Z-isomers are observed with macrocyclic imines. As evident from H-NMR data, azaenolates of cyclodecanone imines generated under these conditions are a mixture of E- and Z-isomers (33 66), whereas azaenolates of cyclododecanone and cyclopenladecanone imines arc formed as the pure. E-isomers (see Table 3). Upon heating the solutions of metalated imines to reflux for 1 hour, complete isomerization to the thermodynamically more stable Z-isomers occurs. 

Included in the class of macrocyclic lactones are avermectins and milbemycins, which are fermentation products possessing a 16-member cyclic lactone, a spiroketal moiety, and a disaccharide unit. Abamycin, ivermectin, doramectin, and eprinomycin are the avermectins most often available for anthelminthic treatment of livestock, whereas moxidectin is a milbemycin with worldwide acclaim as a cattle anthelminthic. Other anthelminthics currently used in food-producing animals are clorsulon, which is a benzenesulphonamide derivative praziquantel, which is a racemate derivative of pyrazino-isoquinoline and hygromycin B, which is an aminoglycoside antibiotic that exhibits anthelminthic properties. 

The 12-membered cyclic tetramines, the smallest tetraaza macrocycles, have a cavity size too... 

The complex [ZnL(H20)2]2+ (L = 2,2,4-trimethyl-l,5,9-triazacyclododecane) loses a proton from an aqua group with a pKa of 9.56.1102 Macrocycles such as (151), with a pyridine group incorporated into the structure, react slowly with Zn2+ compared to other 14-membered cyclic aliphatic tetraaza systems,1103 probably as a result of the rigidity introduced into their structure by the pyridine ring. 

The thermolysis of cobalt complex 116 in the presence of copper powder at 190 °C gave 10-membered cyclic acetylene 117 (Scheme 4) <2002AGE1181>. The reaction was iterated to lead to belt-like macrocycles. The same procedure was also utilized to synthesize twofold CpCo-capped bis(cyclopentadieno)superphane <20000M1578>. 

In addition to the ligands above, considerable attention is given to more complex ligand systems [4,5] aromatic and heteroaromatic compounds (heteroarenes) (i.e., five- or six-member cyclic structures with delocalized 7i-bonds in the ring containing, besides carbon atoms, either N, P, As, O, S, Se, or Te compounds [6-8]), various chelate-forming compounds, such as macrocyclic crown-ethers, cryptands, porphyrins, and phthalocyanines. 

Faill et al. [73, 111] accomplished a U-4CR of a hexapeptide 54 which forms an 18-membered cyclic hexapeptide product 55 (Scheme 4.27). This macrocyclization was not further optimized and proceeded fairly well by the U-4CR. 

The tetraazacycloalkanes, particularly the 14-membered cyclic tetraamine (cyclam) (10), exhibit the macrocyclic effect due to a more favorable enthalpy contribution to complex stability (Hancock and Martell, 1988). Complexes of the pentaaza-crown macrocycles have been studied extensively from a thermodynamic point of view (Bianchi et al., 1991). With the exception of Ni-, [15]Ns formed the most stable complexes with all the metal ions studied with the stability order as follows [15]N5(27) > [16]N5(28) > [17]N3(29) (Bianchi et al., 1991). 

There are critics of the sulfonamide ring closure method. Briellmann and coworkers reported that, although the 9- to 13-membered cyclic trisulfonamides were prepared in 31% to 57% yields, isolation of products was difficult (Briellmann et al., 1987). Up to six products were shown by TLC analysis. Sometimes the impurities could be removed by crystallization, but most often, careful column chromatography was needed. With the larger 11- and 13-membered macrocycles, the 2 2 cyclization products, [22]N(, and [26]Nf were also isolated in 11% and 3% yields, respectively. In the synthesis of the smaller... 

The small contribution of macrocyclization in the polymerization of THF is due to two effects The formation of smaller cyclic oligomers like dimer and trimer is thermodynamically unfavorable (in contrast to the formation of e.g. 1,4-dioxane in the polymerization of ethylene oxide) because 10- and 15-membered cyclic ethers are strained. It is also kinetically hampered since the rate of chain transfer to polymer which leads to ring formation is low due to the lower basicity of the polymer units than that of THF. 

In contrast to the polymerization of four-membered cyclic ethers that yield a large proportion of cycles (predominantly tetramers), macrocycles were not detected in the polymerization of azetidines or thietanes. 

Slow crystallization of 1-trifluoroacetoxybenziodoxaborole 188 from methanol afforded the tetrameric macrocyclic structure 192 resulting from self-assembly of the initially formed 4-fluoro-l,3-dimethoxy-l//-lX -benzoM[l,2,3]iodoxoborole (191) (Scheme 2.59). The structure of macrocycle 192 was established by a single-crystal X-ray analysis [243]. The driving force for formation of the eight-membered cyclic system 192 is the transformation of initial trigonal-planar sp hybrid boron atoms in 191 into tetrahedral sp hybridized atoms. Indeed, each boron atom in tetramer 192 forms one covalent bond with carbon and three covalent... 

Functionalized polyether macrocycles (e.g., 1) were prepared (<60%) by the Rh(ll)-catalyzed decomposition of methyl diazoacetoacetate in the presence of substituted or unsaturated 5- and 6-membered cyclic ethers (13ASC3161). A supramolecular organogel was prepared by mixing two different glycidyl... 

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